Gene Regulation in Breast Cancer

Estrogen and progesterone are master regulators of numerous physiological processes including mammary development and reproduction. They are also intricately linked to the development of breast cancer. Whereas the tumor-promoting role of estrogen has been well established, progesterone can exert both pro- and anti-tumoral effect depending on the cellular and clinical context. Our research focuses primarily on the understanding of molecular mechanisms that regulate cell context- and gene-specific activity of progesterone receptor with the goal of identifying molecular markers that predict anti-tumoral response to progestin in breast cancer. We are particularly interested in how the intrinsically structured activation function 1 is involved in the diverse function of progesterone receptor and have established genetic models to define the AF1-mediated response to progestin. We are also interested in how estrogen receptor regulates the context-dependent activity of progesterone receptor. ​
Valerie LinLEAD PI
Lin Chun Ling Valerie
Associate Professor, School of Biological Sciences
Deputy Director, NTU Chinese Medicine Clinic

Email: [email protected]
Phone: (65) 6316 2843
Office: SBS-03N-08
Leong Kye Siong
Project Officer

Email: [email protected]
Low Ying Bei, Clara
Masters Stu​dent

Email: [email protected]


  1. Plasticity of estrogen action on mammary neutrophils during development.
  2. Role of activation function 1 of progesterone receptor in gene regulation.
  1. Chew Leng Lim, Yu Zuan Or, Zoe Ong, Hwa Hwa Chung, Hirohito Hayashi, Smeeta Shrestha, Shunsuke Chiba, Feng Lin, Valerie CL Lin (2020) Estrogen exacerbates mammary involution through neutrophil dependent and independent mechanisms. eLife 9:e57274.
  2. Li Quan, Wing Shan Yu, Smeeta Shrestha, Yu Zuan Or, Thomas Lufkin, Ying-Shing Chan, Valerie CL Lin and Lee Wei Lim (2020) TTC9A deficiency induces estradiol-mediated changes in hippocampus and amygdala neuroplasticityrelated gene expressions in female mice. Brain Research Bulletin, 157: 162-168.
  3. Tan SJ, BAJALOVIC N, Wong SP and Lin VCL (2019) Ligand-activated progesterone receptor B activates Transcription Factor EB to promote autophagy in MCF-7 human breast cancer cells. Experimental Cell Research. 382(1):111433.
  4. Woo AR, Sze SK, Chung HH, Lin VCL (2019) Delineation of critical amino acids in activation function 1 of progesterone receptor for recruitment of transcription coregulators. Biochim Biophys Acta Gene Regul Mech, 1862(4):522-533.
  5. Venkatesan N., Wong JF., Tan PK. , Chung WW., Yau YH., Cukuroglu E., Allahverdi A., Nordenskiold L., Göke J., Shochat SG., Lin C-L.V., Madhusudhan MS., and Su I-H. (2018), VAV interaction-dependent extranuclear function of EZH2 controls neoplastic transformation. Oncogene, 37(4):461-477.
  6. Hwa Hwa Chung, Yu Zuan Or, Smeeta Shrestha, Jia Tong Loh, Chew Leng Lim, Zoe Ong, Amanda Rui En Woo, I-Hsin Su, Valerie C-L Lin (2017) Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution. Scientific Reports, 7 (46485).
  7. Lim L.W., Shrestha S., Or Y.Z., Tan S.Z.K., Chung H.H., Sun Y., Lim C.L., Khairuddin S., Lufkin T., Valerie C. L. Lin. (2016) Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice. Scientific Reports, 6 (37568).
  8. Wan Z.Y., Xia J.H., Lin G., Wang L., Valerie C. L. Lin, Yue G.H. (2016) Genome-wide methylation analysis identified sexually dimorphic methylated regions in hybrid tilapia Scientific Reports, 6 (35903).
  9. Shrestha S, Sun Y, Lufkin T, Kraus P, Or Y, Garcia YA, Guy N, Ramos P, Cox MB, Tay F, Valerie C. L. Lin (2015) Tetratricopeptide Repeat Domain 9A Negatively Regulates Estrogen Receptor Alpha Activity. Int J Biol Sci. 11(4):434-47.
  10. Sun Y, Chung HH, Woo AR, Valerie C. L. Lin (2014) Protein Arginine Methyltransferase 6 Enhances Liganddependent and -independent Activity of Estrogen Receptor α via Distinct Mechanisms. BBA - Molecular Cell Research, 1843(9):2067-78.